Field of the Invention
The present invention relates to a bidirectional alternating magnetic field application system for preventing or treating brain tumor and to a method for applying magnetic field using the same. Moreover, the present invention relates to a method for treating or preventing brain tumor, in which a bidirectional alternating magnetic field application system that generates a weak magnetic field is used to specifically inhibit the proliferation of malignant brain glioma cells and reduce the mobility thereof without causing damage to normal cells.
Description of the Prior Art
Malignant brain glioma is a kind of cancer disease that occurs when glial cells in the brain develop into cancer cells. More than half of gliomas are malignant, and even benign gliomas show a tendency to develop into malignancy with the passage of time. About 60% of cancers that develop in the brain are malignant gliomas, and the incidence thereof not only in the USA and Europe but also in Korea is increasing. Malignant glioma rapidly metastasizes as cancer cells rapidly penetrate the surrounding tissues. Unlike other cancers, malignant glioma is a disease requiring immediate medical remedy, since glial cells, which develop into malignancy rapidly even without differentiation between phases 1 and 2, penetrate the surrounding brain tissues, causing palsy, convulsion, headache or, disorders of consciousness.
Malignant glioma can be diagnosed by computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) or the like, which is used to measure tumor characteristics (e.g., location, area and malignancy).
General methods for brain tumor treatment, which are currently performed in clinical hospitals, include tumor removal surgery, radiotherapy and anticancer chemotherapy. Tumor removal surgery is a method for removing tissues developed into malignant glioma. It can minimize the volume of tumor, and thus can substantially reduce problems such as an increase in brain pressure, which occurs in some tumors. However, malignant glioma tissue has characteristics in that its boundary with normal tissue is unclear and it grows at a very high rate. Due to such characteristics, in many cases, it is impossible to completely remove the malignant glioma tissue by surgery. For this reason, for most malignant glioma patients, it is required to take continuous radiotherapy and anticancer chemotherapy therapy in combination even after surgery. Radiotherapy is a therapeutic method that is applied to exterminate tumor cells capable of remaining after tumor removal surgery and to delay the growth of the tumor cells. In radiotherapy, a total of about 60 Gy of radiation dose is irradiated in divided doses over 6-7 weeks. However, radiotherapy also affects normal proliferating cells, resulting in side effects such as salivary gland damage or hair loss. Anticancer chemotherapy is a therapeutic method that is applied to exterminate tumor cells remaining after tumor removal surgery and to delay the growth of the tumor cells. Standard anticancer chemotherapy is carried out with Temozolomide approved by the FDA, but causes side effects such as vomiting, giddiness, headache, a decrease of appetite, physical degradation, or temporary hair loss. In the case of elderly patients, tumor tissue removal surgery is not performed in order to reduce burden on the body, but it is general to perform radiotherapy and chemotherapy in combination. However, even when this combination therapy is applied to brain tumor patients, the mean survival time of these brain tumor patients is 12-15 months, and the survival rate of the patients is low even when the patients are treated with surgery and other therapies. In addition, when tumor cells penetrate tissue and are present therein, the possibility of recurrence of the tumor is high. As described above, malignant glioma is a disease having a very high possibility of recurrence even after surgery and difficult to cure completely.
Meanwhile, there were attempts to treat malignant glioma using a magnetic field. Korean Patent Application No. 2009-0078310 discloses a method for inhibiting cancer cell growth using a magnetic field (Patent Document 1). Patent Document 1 is characterized in that a unidirectional magnetic field having a strong intensity (2,000 Gauss (0.2 T)), generated from a direct current system comprising a permanent magnet or an electromagnet is applied. However, in this method, there is a high risk of damage to normal cells due to strong magnetic field intensity. In addition, PCT publication no. WO2013/121359 discloses a method for treating brain disease using a transcranial magnetic stimulation device, particularly a pulse magnetic field (Patent Document 2). Another prior art discloses a method for treating malignant glioma using magnetic nanoparticles (Non-Patent Document 1: Andreas Jordan et al.). Non-Patent Document 1 relates to a thermal therapy employing a high frequency of 100 kHz. However, in these conventional technologies, damage to normal cells is greatly doubtful, because a magnetic field having a very strong intensity in a high frequency range is applied in order to inhibit the proliferation of tumor cells. In addition, these conventional technologies do not propose a solution to the problem of inhibition of the metastasis of glial cells to the surrounding tissue, which is the most important problem in the treatment of malignant glioma.
Accordingly, the present inventors have surprisingly found that, when a bidirectional alternating magnetic field is generated and applied to malignant gioma cells, the proliferation of the malignant glial cells is effectively inhibited in a frequency range significantly lower than those used in the conventional technologies, thereby completing the present invention. In addition, the present invention enables only malignant glioma cells to be specifically inhibited without causing damage to normal cells, and can reduce the mobility of these glioma cells to thereby effectively inhibit the metastasis of brain tumor.